Bayer Charged With Burying Negative VTE Data for Yasmin

WASHINGTON -- A former FDA commissioner accused Bayer of hiding data on the blood clot risks associated with two of its birth control pills, Yasmin and Yaz, and engaging in "extensive" off-label promotion in order to increase sales.

The accusations, from David Kessler, MD, were contained in an expert opinion that was unsealed this week by a federal court in Illinois. There are currently multiple lawsuits pending over injuries and deaths related to drospirenone/ethinyl estradiol tablets (Yasmin and Yaz) and generic versions of the pills.

"By failing to disclose all thromboembolic event risk information and marketing Yaz and Yasmin off-label, Bayer needlessly exposed large numbers of women to risks of serious or fatal thromboembolic events," Kessler concluded in his 196-page opinion.

The unsealing of the document comes just before the FDA's Reproductive Health Drugs Advisory Committee is slated to hold a Thursday meeting to discuss the risks and benefits of oral contraceptives containing drospirenone:

Drospirenone/ethinyl estradiol tablets (Yasmin and Yaz)

Drospirenone/ethinyl estradiol/levomefolate calcium tablets (Beyaz)

Levomefolate calcium tablets (Safyral)

All generic versions

On Friday, the same committee will discuss the blood clot risk and the benefits of norelgestromin/ethinyl estradiol transdermal system (Ortho Evra) marketed by Janssen Pharmaceuticals.

In his written opinion, Kessler accused Bayer of omitting data on thrombotic events in the review the company submitted to the FDA. Specifically, he said the company wrote a draft of a white paper in 2004 that stated Yasmin had a "several-fold increase" in rates of deep vein thrombosis, pulmonary embolism, and confirmed venous thromboembolism (VTE) compared with three other common birth control pills.

Also, serious adverse events were 10 times higher for Yasmin than for other similar products.

But a final version of the white paper submitted to the FDA stated that: "The spontaneous reporting data do NOT signal a difference in VTE rates for Yasmin and other [oral contraceptive] uses. We see NO signal of a difference." There was no additional data added to support that claim, Kessler said.

The earlier information about the data revealing a link to increased thrombotic events was entirely omitted from the final white paper Bayer submitted to the FDA in 2004.

"It appears, based on the information that I have reviewed, and it is my opinion, that Bayer presented a selective view of the data, and that presentation obscured the potential risks associated with Yasmin," Kessler wrote. "In my opinion, Bayer had a duty to present a full and balanced view of all the data and analysis concerning Yasmin to the FDA and healthcare professionals and failed to do so."

Kessler also claimed that Bayer carried out a "systematic and extensive campaign to market Yasmin and Yaz" as a treatment for premenstrual syndrome (PMS) and acne even though the products weren't approved for those indications. In addition, the company repeatedly overstated the benefits of the pills and downplayed their risks, Kessler said.

"Bayer engaged in extensive, systematic off-label promotion of Yasmin and YAZ for PMS, in violation of FDA law and regulations, thereby unnecessarily exposing large numbers of women to risk of thromboembolic events, in violation of state law duties," Kessler wrote in opinion.

Kessler also claimed Bayer ghost-wrote articles on Yasmin (approved in 2001) and Yaz (approved in 2006) for publication in medical journals, and that Bayer promoted off-label use of its birth control pills through continuing medical education.

Rose Talarico, a spokeswoman for Bayer said the company "has nothing further to add as these are matters of litigation." She said Bayer expects the issues to be addressed at trial.

The newly-unsealed documents likely will not be a part of the FDA hearing because the deadline has passed to submit documents for the advisory committee.

Blood clots are a known side effect of all birth control pills, but two recent studies out of the U.S. and the U.K., suggested the risk of VTE associated with oral contraceptives that contain drospirenone was double or triple that of another common contraceptive hormone, levonorgestrel.

Thursday's advisory committee will be asked to consider the conflicting data on drospirenone-containing pills, the benefits and risks of the pills, and whether current labels accurately reflect those risks and benefits.

In briefing documents released ahead of the meeting, FDA reviewers said, "review of the epidemiologic studies show certain trends that cannot be ignored," including that newly-approved combination hormonal contraceptives appear to have a higher risk for VTE than older versions. Studies from the drug manufacturers showed no increased risk.

In Bayer's briefing documents, the company said trials to assess the risk of VTE "provide strong evidence that the risk" associated with Yasmin and Yaz is similar to the other combination oral contraceptives.

"The current body of rigorous scientific evidence strongly supports a favorable benefit-risk profile for [drospirenone]-containing [combination oral contraceptives] when used in accordance to labeling," the company said.

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